Advertisement

Bipolar disorder in the balance

  • Brian J. LithgowEmail author
  • Zahra Moussavi
  • Caroline Gurvich
  • Jayashri Kulkarni
  • Jerome J. Maller
  • Paul B. Fitzgerald
Original Paper

Abstract

Bipolar disorder (BD) is a severe mood disorder that lacks established electrophysiological, neuroimaging or biological markers to assist with both diagnosis and monitoring disease severity. This study’s aim is to describe the potential of new neurophysiological features assistive in BD diagnosis and severity measurement utilizing the recording of electrical activity from the outer ear canal called Electrovestibulography (EVestG). From EVestG data sensory vestibulo-acoustic features were extracted from a single supine-vertical translation stimulus to distinguish 50 depressed and partly remitted/remitted bipolar disorder patients [18 symptomatic (BD-S, MADRS > 19), 32 reduced symptomatic (BD-R, MADRS ≤ 19)] and 31 age and gender matched healthy individuals (controls). Six features were extracted from the measured firing pattern interval histogram and the extracted shape of the average field potential response. Five of the six features had low but significant correlations (p < 0.05) with the MADRS assessment. Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 75–79%, 84–86%, 76–85% and 79–82% accuracy for separation of control from BD, BD-S and BD-R as well as BD-S from BD-R groups, respectively. The main limitation of this study was the inability to fully disentangle the impact of prescribed medication from the responses recorded. A mix of stationary and movement evoked EVestG features produced good discrimination between control and BD patients whether BD-S or BD-R. Moreover, BD-S and BD-R appear to have measurably different pathophysiological manifestations. The firing pattern features used were dissimilar to those observed in a prior major depressive disorder study.

Keywords

Bipolar disorder Depression Neurobiology Electrovestibulography Biological markers Vestibular 

Abbreviations

AD

Antidepressant medication

AMPA

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Background phase

1.5 s EVestG recording immediately prior to motion

BD

Bipolar disorder, (-S) symptomatic, (-R) reduced symptomatic (-R can be broken into (-M) mild and (-A) asymptomatic)

EVestG

Electrovestibulography

FP

Field potential

IH1, IH2

EVestG short interval features. Intervals were the time between detected FP’s

IH331, IH332

EVestG long interval features. Intervals were the time between each 33rd FP

LDA

Linear discriminant analysis

MADRS

Montgomery Asberg Depression Rating Scale

MDD

Major depressive disorder, (-S) symptomatic, (-R) reduced symptomatic

MS

Mood stabilizer medication

NDMA

N-methyl-d-aspartate

AP

Antipsychotic medication

NEER

Neural event extraction routine

NM

No-medication

NPC

Non-parametric classifier

Acceleration phase

1.5 s EVestG recording during the acceleration phase

Deceleration phase

1.5 s EVestG recording during the deceleration phase

Sh1, Sh2

EVestG shape features

Notes

Acknowledgements

We would like to thank all members of Monash Alfred Psychiatry Research Center who supported this research. Amber Garrett (a Ph.D. student) recorded many of the EVestG recordings. This work was supported by grants from the Australian Research Council and National Health and Medical Research Council. Neural Diagnostics Pty Ltd was the industry partner in this research. PF is supported by an NHMRC practitioner fellowship.

Author contributions

BL wrote the first draft and did main data analysis; ZM and PF were the major contributors to the data analysis and paper writing; BL, PF, JK and CG conceived the experiment(s). PF and JK examined and referred the patients. CG and JM contributed to patient assessments. All authors reviewed the manuscript.

Funding

Funding was provided by Australian Research Council (Grant no. LP0669420).

Compliance with ethical standards

Conflict of interest

BL owns < 0.5% of shares in Neural Diagnostics Pty Ltd. (ND) and acts as a part-time consultant for ND. PF is supported by a NHMRC Practitioner Fellowship (1078567). PF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Neuronetics and Cervel Neurotech. He is on the scientific advisory board for Bionomics Ltd. ZM, CG, JM, JK report no financial interests or potential conflicts of interest.

Supplementary material

406_2018_935_MOESM1_ESM.docx (101 kb)
Supplementary material 1 (DOCX 100 KB)

References

  1. 1.
    Ghaemi SN, Boiman EE, Goodwin FK (2000) Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry 61:804–808CrossRefPubMedGoogle Scholar
  2. 2.
    Ghaemi SN, Sachs GS, Chiou AM, Pandurangi AK, Goodwin K (1999) Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord 52:135–144CrossRefPubMedGoogle Scholar
  3. 3.
    Rosa AR, Andreazza AC, Kunz M, Gomes F, Santin A, Sanchez-Moreno J et al (2008) Predominant polarity in bipolar disorder: diagnostic implications. J Affect Disord 107(1–3):45–51CrossRefPubMedGoogle Scholar
  4. 4.
    Lithgow BJ, Garrett AL, Moussavi ZM, Gurvich C, Kulkarni J, Maller JJ et al (2015) Major depression and electrovestibulography. World J Biol Psychiatry 16(5):334–350CrossRefPubMedGoogle Scholar
  5. 5.
    Schmitt A, Falkai P (2013) Differential diagnosis of major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 263(2):83–84CrossRefPubMedGoogle Scholar
  6. 6.
    Gurvich C, Maller JJ, Lithgow B, Haghgooie S, Kulkarni J (2013) Vestibular insights into cognition and psychiatry. Brain Res 1537:244–259CrossRefPubMedGoogle Scholar
  7. 7.
    Marlinsky V (1995) The effect of somatosensory stimulation on second-order and efferent vestibular neurons in the decerebrate decerebellate guinea-pig. Neuroscience 69:661–669CrossRefPubMedGoogle Scholar
  8. 8.
    Li C, Zhang Y, Guan Z, Shum DKY, Chan Y (2005) Vestibular afferent innervation in the vestibular efferent nucleus of rats. Neurosci Lett 385:36–40CrossRefPubMedGoogle Scholar
  9. 9.
    Wang J, Chi F, Xin Y, Regner MF (2013) The distribution of vestibular efferent neurons receiving innervation of secondary vestibular afferent nerves in rats. Laryngoscope 123(5):1266–1271CrossRefPubMedGoogle Scholar
  10. 10.
    Balaban CD, Jacob RG, Furman JM (2011) Neurologic bases for comorbidity of balance disorders, anxiety disorders and migraine: neurotherapeutic implications. Expert Rev Neurother 11(3):379–394CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hegerl U, Herrmann WM, Ulrich G, Muller-Oerlinghausen B (1990) Effects of lithium on auditory evoked potentials in healthy subjects. Biol Psychiatry 27:555–560CrossRefPubMedGoogle Scholar
  12. 12.
    Fisman M (1975) Superior olivary complex in psychotic patients. Psychol Med 5(2):147–151CrossRefPubMedGoogle Scholar
  13. 13.
    Vlaski L, Dragicević D, Dankuc D, Kljajić V, Lemajić-komazec S, Komazec Z (2008) Psychogenic hearing impairment in differential diagnosis of sudden hearing loss. Med Pregl 61(Suppl 2):31–35PubMedGoogle Scholar
  14. 14.
    Hasson D, Theorell T, Benka Wallén M, Leineweber C, Canlon B (2011) Stress and prevalence of hearing problems in the Swedish working population. BMC Public Health 11:130CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Horner KC (2003) The emotional ear in stress. Neurosci Biobehav Rev 27(5):437–446CrossRefPubMedGoogle Scholar
  16. 16.
    Pinto PC, Marcelos CM, Mezzasalma MA, Osterne FJ, de Melo Tavares de Lima MA, Nardi AE (2014) Tinnitus and its association with psychiatric disorders: systematic review. J Laryngol Otol 128(8):660–664CrossRefPubMedGoogle Scholar
  17. 17.
    Paulin J, Andersson L, Nordin S (2016) Characteristics of hyperacusis in the general population. Noise Health 18(83):178–184CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Marriage J, Barnes MM (1995) Is central hyperacusis a symptom of 5-hydroxytryptamine (5-HT) dysfunction? J Laryngol Otol 109(10):915–921CrossRefPubMedGoogle Scholar
  19. 19.
    Lithgow BJ (2012) A methodology for detecting field potentials from the external ear canal: NEER and EVestG. Ann BME 40(8):1835–1850Google Scholar
  20. 20.
    Blakley B, Suleiman A, Rutherford G, Moussavi Z, Lithgow BJ (2018) EVestG recordings are vestibuloacoustic signals. J Med Biol Eng.  https://doi.org/10.1007/s40846-018-0398-6 CrossRefGoogle Scholar
  21. 21.
    Suleiman A, Lithgow B, Dastgheib Z, Mansouri B, Moussavi Z (2017) Quantitative measurement of post-concussion syndrome (PCS) using Electrovestibulography (EVestG). Sci Rep (Nature).  https://doi.org/10.1038/s41598-017-15487-2 CrossRefGoogle Scholar
  22. 22.
    Lithgow BJ, Shoushtarian M (2015) Parkinson’s disease: disturbed vestibular function and Levodopa. J Neurol Sci 353(1–2):49–58CrossRefPubMedGoogle Scholar
  23. 23.
    Dastgheib Z, Lithgow BJ, Blakley B, Moussavi Z (2014) A new diagnostic vestibular evoked response. J Otolaryngol Head Neck Surg 44(1):14CrossRefGoogle Scholar
  24. 24.
    Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry J Ment Sci 134:382–389CrossRefGoogle Scholar
  25. 25.
    Heibert D (2010) Computer models of the vestibular head tilt response, and their relationship to EVestG and Meniere’s disease. Doctor of Philosophy, Monash UniversityGoogle Scholar
  26. 26.
    Soza Ried AM, Aviles M (2007) Asymmetries of vestibular dysfunction in major depression. Neuroscience 144(1):128–134CrossRefPubMedGoogle Scholar
  27. 27.
    Soza AM, Barroilhet S, Vohringer PA (2017) A vestibular biomarker of manic and depressive phase in bipolar disorder. Asia Pac J Clin Trials Nerv Syst Dis 2(4):140–145CrossRefGoogle Scholar
  28. 28.
    Brown DJ, Patuzzi RB (2010) Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater. Hear Res 267:12–26CrossRefPubMedGoogle Scholar
  29. 29.
    McLachlan GJ (1992) Discriminant analysis and statistical pattern recognition. Wiley, New YorkCrossRefGoogle Scholar
  30. 30.
    Niculescu AB (2013) Convergent functional genomics of psychiatric disorders. Am J Med Genet Part B 9999:1–7Google Scholar
  31. 31.
    Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB et al (2003) Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362(9386):798–805CrossRefPubMedGoogle Scholar
  32. 32.
    Davis KL, Haroutunian V (2003) Global expression-profiling studies and oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362(9386):758CrossRefPubMedGoogle Scholar
  33. 33.
    Soreff S (2013) Medscape: bipolar disorder-etiology and pathophysiology. http://emedicine.medscape.com/article/286342-overview#a0104. Accessed 14 Mar 2014
  34. 34.
    Soto E, Vega R (2010) Neuropharmacology of vestibular system disorders. Curr Neuropharmacol 8:26–40CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Thomsen MS, Weyn A et al (2011) Hippocampal a7 nicotinic acetylcholine receptor levels in patients with schizophrenia, bipolar disorder, or major depressive disorder. Bipolar Disord 13:701–707CrossRefPubMedGoogle Scholar
  36. 36.
    Cannon DA, Carson RE et al (2006) Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder. Arch Gen Psychiatry 63:741–747CrossRefPubMedGoogle Scholar
  37. 37.
    Anderson AD, Troyanovskaya M, Wackym PA (1997) Differential expression of alpha2-7, alpha9-10 and beta2-4 nicotinic acetylcholine receptor subunit mRNA in the vestibular end organs and Scarpa’s ganglia of the rat. Brain Res 778:409–413CrossRefPubMedGoogle Scholar
  38. 38.
    Philip NS, Carpenter LS (2012) The nicotinic acetylcholine receptor as a target for antidepressant drug development. Sci World J 2012:1–7 (Article ID 104105) CrossRefGoogle Scholar
  39. 39.
    Wackym PA, Chen T, Ishyama A, Pettis RM, Lopez IA, Hoffman L (1996) Muscarinic acetylcholine receptor subtype in mRNA’s in the human and rat vestibular periphery. Cell Biol Int 20(3):187–192CrossRefPubMedGoogle Scholar
  40. 40.
    Guo C, Wang Y, Zhou T, Yu H, Zhang W-J, Kong W-J (2012) M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II hair cells. Hear Res 285:13–19CrossRefPubMedGoogle Scholar
  41. 41.
    Zhu Y, Chen SR, Pan HL (2016) Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons. J Neurochem 137(2):226–239CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Bitner RS, Nikkel AL (2002) Alpha-7 nicotinic receptor expression by two distinct cell types in the dorsal raphe nucleus and locus coeruleus of rat. Brain Res 938(1–2):45–54CrossRefPubMedGoogle Scholar
  43. 43.
    Egan TM, North RA (1985) Acetylcholine acts on m2-muscarinic receptors to excite rat locus coeruleus neurones. Br J Pharmacol 85(4):733–735CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Pérez C, Limón A, Vega R, Soto E (2009) The muscarinic inhibition of the potassium M-current modulates the action potential discharge in the vestibular primary-afferent neurons of the rat. Neuroscience 158:1662–1674CrossRefPubMedGoogle Scholar
  45. 45.
    Drevets WC, Furey ML (2010) Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry 67(5):432–438CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Benes FM (2012) Nicotinic receptors and functional regulation of GABA cell microcircuitry in bipolar disorder and schizophrenia. In: Geyer MA, Goss G (eds) Handbook of experimental pharmacology: novel antischizophrenia treatments, vol 213. Springer, BerlinGoogle Scholar
  47. 47.
    Luscher BE, Shen Q, Sahir N (2011) The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16(4):383–406CrossRefPubMedGoogle Scholar
  48. 48.
    Cortes C, Calindo F, Galicia S, Cebada J, Flores A (2013) Excitatory actions of GABA in developing chick vestibular afferents: effects on resting electrical activity. Synapse 67(7):374–381CrossRefPubMedGoogle Scholar
  49. 49.
    Yadav R, Gupta SC, Hillman BG, Bhatt JM, Stairs DJ, Dravid SM (2012) Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviours. PLoS ONE 7(3):e32969CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Soto E, Flores A, Erostegui C, Vega R (1994) Evidence for NMDA receptor in the afferent synaptic transmission of the vestibular system. Brain Res 633:289–296CrossRefPubMedGoogle Scholar
  51. 51.
    Dememes D, Lleixa A, Dechesne CJ (1994) Cellular and subcellular localization of AMPA-selective glutamate receptors in the mammalian peripheral vestibular system. Brain Res 671:83–94CrossRefGoogle Scholar
  52. 52.
    Dieterich M, Bense S, Lutz S, Drzezga A, Stephan T, Bartenstein P et al (2003) Dominance for vestibular cortical function in the non-dominant hemisphere. Cereb Cortex 13(9):994–1007CrossRefPubMedGoogle Scholar
  53. 53.
    Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE (2005) Lifetime prevalence and age-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62(6):593–602CrossRefPubMedGoogle Scholar
  54. 54.
    Hirschfeld RM, Lewis L, Vornik LA (2003) Perceptions and impact of bipolar disorder. J Clin Psychiatry 64(2):161–174CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Monash Alfred Psychiatry Research CentreMonash University Central Clinical School and The Alfred HospitalMelbourneAustralia
  2. 2.Diagnostic and Neurosignal Processing Research Laboratory, Riverview Health CentreUniversity of ManitobaWinnipegCanada

Personalised recommendations